Abstract
BackgroundThis study investigates the effect of letrozole on hormone profiles, semen parameters, body mass index (BMI), degree of oxidative stress and sperm chromatin integrity in men with idiopathic oligo/astheno/teratozoospermia (iOAT) and T:E2 ratio ≤ 10.Materials and methodsThis study is a longitudinal, prospective, interventional and open-labelled clinical trial. Semen samples were collected from 20 iOAT men with low serum testosterone (T) to estradiol (E2) ratio (T:E2 ratio ≤ 10). The participants were treated with 2.5 mg letrozole orally per day for 3 months. Then, sperm parameters, hormone profiles, BMI, chromatin integrity and intracellular reactive oxygen species (ROS) level were assessed pre- and post- treatment. The chromatin integrity was evaluated by assessment of DNA fragmentation (with TUNEL assay) and protamine deficiency (with Chromomycin A3, CMA3). Also, the intracellular ROS levels were investigated by 2′, 7′-dichlorodihydrofluorescein diacetate (DCFH-DA) staining. Finally, the differences between the parameters evaluated before and after letrozole treatment were analyzed with the t-test and the Wilcoxon signed-rank test.ResultsSperm concentration, percentage of sperm motility and its normal morphology increased significantly after letrozole treatment. Moreover, serum testosterone level increased but estradiol level decreased significantly following treatment. The mean of T:E2 ratio improved 1600%. Also, letrozole treatment significantly reduced the percentage of sperm TUNEL positivity and sperm CMA3 positivity. While no significant difference was observed between intracellular ROS levels and BMI before and after treatment. Finally, as a notable result, four spontaneous pregnancies (20%) were achieved after treatment.ConclusionsLetrozole treatment can effectively increase spontaneous pregnancies by improving sperm parameters and sperm chromatin integrity in men with iOAT and T:E2 ratio ≤ 10.Trial registrationTrial registration: IRCT, IRCT20191030045283N1. Registered 16 November 2019 - Retrospectively registered, https://fa.irct.ir/user/trial/43484/view
Highlights
This study investigates the effect of letrozole on hormone profiles, semen parameters, body mass index (BMI), degree of oxidative stress and sperm chromatin integrity in men with idiopathic oligo/astheno/ teratozoospermia and T:E2 ratio ≤ 10
In this study, 20 participants with idiopathic oligo/astheno/ teratozoospermia (iOAT) and serum T:E2 ratio ≤ 10 were treated with letrozole for 3 months
These infertile men were evaluated for semen parameters, hormone profiles, BMI, sperm DNA fragmentation, protamine deficiency and sperm intracellular reactive oxygen species (ROS) level pre-and post-treatment
Summary
This study investigates the effect of letrozole on hormone profiles, semen parameters, body mass index (BMI), degree of oxidative stress and sperm chromatin integrity in men with idiopathic oligo/astheno/ teratozoospermia (iOAT) and T:E2 ratio ≤ 10. A number of factors may be involved in the genesis of this condition, including age [4], non-inflammatory alterations in the function of post testicular organs like prostate [5, 6], infective agents [7], environmental disturbances [8, 9], subtle hormonal anomalies and genetic and epigenetic factors [8]. Considering these probable etiologies, opportunities have been provided for further research in new approaches of empirical medical therapy. Based on such observations, aromatase inhibitors (especially letrozole) have gained much attention for the treatment of iOAT with T:E2 ratio ≤ 10 [15,16,17,18,19]
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